Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma

The walls of pulmonary capillaries are extremely thin, and wall stress increases greatly when capillary pressure rises. Alveolar hypoxia causes pulmonary vasoconstriction and hypertension, and if this is uneven, some capillaries may be exposed to high transmural pressure and develop stress failure. There is evidence that increased wall stress causes capillary remodeling. In this study we exposed Madison strain Sprague-Dawley rats to normobaric hypoxia (10% oxygen) for 6 h or 3 d (short-term group), and for 3 d or 10 d (long-term group). Peripheral lung tissue was then collected and messenger RNA (mRNA) levels were determined for extracellular matrix (ECM) proteins and growth factors. Collagen content (hydroxyproline) was also measured. Levels of mRNA for alpha2(IV) procollagen increased sixfold after 6 h of hypoxia and sevenfold after 3 d of hypoxia, and then decreased after 10 d exposure. Levels of mRNA for platelet-derived growth factor-B (PDGF-B) doubled after 6 h of hypoxia but returned to control values after 3 d. mRNA levels for alpha1(I) and alpha1(III) procollagens and fibronectin were increased after 3 d of hypoxia (by seven- to 12-fold, 1.6- to eightfold, and 12-fold, respectively), then decreased toward control values after 10 d. In contrast, neither levels of mRNA for vascular endothelial growth factor (VEGF) nor collagen content changed. These results suggest that alveolar hypoxia causes vascular remodeling in lung parenchyma, and are consistent with capillary wall remodeling in response to increased wall stress.     

Chronic exposure of rats to hypoxic environment alters the mechanism of energy transfer in myocardium

We have investigated the effect of chronic exposure of rats to an hypoxic environment (10% O2; 3 weeks), on the first step of the intracellular energy transfer process in the myocardium, i.e. the transfer at mitochondrial level of high energy bonds from ATP to creatine. In the left ventricles from rats adapted to normobaric hypoxia, we observed, using the permeabilized fiber technique, that the stimulatory effect of creatine on the mitochondrial respiration in presence of a low ADP concentration (0.1 mM) was attenuated when compared to control. Furthermore, the creatine-induced decrease of the apparent K(m) for ADP of the mitochondrial respiration, which is observed in control, was significantly reduced. Both the basal and maximal respiratory rates of the fibers were unchanged by the hypoxic exposure of the rats. A significant decrease of the total creatine kinase activity from 755 to 630 IU/g wet weight (for control and hypoxic rats, respectively) was detected and was accompanied by a 25% decrease in mitochondrial isoform activity (mitoCK) and in the mitoCK/citrate synthase ratio. In the right ventricles, identical alterations in the effect of creatine on apparent K(m) for ADP were observed while we did not detect any changes in CK activity. The decrease in mitoCK activity and the fall in the reactivity of respiration to creatine could be interpreted as a mechanism for downregulating oxygen demand during chronic hypoxia. The consequences of such alterations on energy metabolism of cardiomyocytes under conditions of reduced oxygen supply are discussed.     

Bone marrow oxygen consumption and erythropoiesis in chronically hypoxic rats

Bone marrow oxygen consumption (VO2) was determined weekly in 16 Holtzman rats exposed to continuous hypobaric hypoxia (CHH) during 30 days. The results were compared with those obtained in 10 sea level control animals (SL). The VO2 expressed as ng.at.O2/min, decreased progressively with time of exposure to hypoxia. VO2 (mean +/- SD) was 0.0936 +/- 0.135 in SL rats. In CHH animals, it was 0.1001 +/- 0.0292 after 8 days of hypoxia, 0.1030 +/- 0.0206 after 16 days, 0.0594 +/- 0.0148 (p = 0.002) after 24 days and 0.0136 +/- 0.404 (p = 0.000) after 30 days. Protein concentration in bone marrow was progressively higher in hypoxics when compared to control, with significant differences since the first week of exposure. Blood hemoglobin increased in parallel to protein concentration in the bone marrow. These findings suggest an increase in the cells of the erythroid series whose oxygen consumption is less than cells in the early stages of differentiation. The increased protein concentration is in agreement with the fact that globin mRNA appears in cells with a progressively increasing anaerobic metabolism at relatively late stages of erythropoiesis.     

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.     

Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats

The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.     

Hemodynamic effects of short-term noise exposure--comparison of steady state and intermittent noise at several sound pressure levels

The purpose of the present study was to investigate the extent of blood pressure elevation during noise exposure, to elucidate the underlying hemodynamic mechanisms and to assess baroreceptor cardiac reflex sensitivity in connection with blood pressure elevation. Twenty-two young normotensive males participated in the experiment and underwent six noise exposure conditions of 20 min each: steady state and intermittent pink noises of 80 dB (sound pressure level (SPL)), 90 dB (SPL) and 100 dB (SPL). The results indicate that elevations in mean arterial pressure, as well as diastolic and systolic blood pressure, were significant or almost significant in the intermittent 100 dB (SPL) and 90 dB (SPL) conditions. Habituation occurred particularly with the steady state noises. In at least the intermittent 100 dB (SPL) condition, an increase in peripheral vascular resistance was the underlying hemodynamic mechanism of blood pressure elevation. Decreases in cardiac output and stroke volume were also associated with the peripheral vasoconstriction. Baroreceptor reflex sensitivity was maintained near the baseline level for all of the noise exposure conditions. Therefore, reflex sensitivity may not have been suppressed even in the intermittent 100 dB (SPL) condition during which blood pressure elevations occurred.     

Verification and determination of opiates in the urine and blood with thin-layer chromatography followed by densitometry in fatal cases of drug abuse

This article shows that in oxygen transported and antioxidative systems considerable changes take place during dynamic of adaptation to oxygen deficiency of inhaled air (every day 4 hours stay of animals in barochamber under pO2 7.45 kPa during 12 days). Single influence of hypoxic factor induced in erythrocytes peripheral blood increasing of haemoglobin affinity to oxygen, decreasing SOD and catalase activity on the background of increasing of malon aldehyde level. On 12-th day of adaptation of animals contents of TBA-active products in erythrocytes is saved on high level, activity of antioxidative enzymes is approached to original meanings, haemoglobin affinity to oxygen is decreased in comparison with control. Detected increasing content of creatine in erythrocytes during dynamic of rat adaptation to hypoxic hypoxia witnessed about erythropoiesis activation and quickened exit out of marrow young forms of erythrocytes.     

Haemolytic uraemic syndrome complicated by disseminated extraneural cryptococcosis

INTRODUCTION: Syncope at altitude of otherwise healthy individuals is a well-known phenomenon (22). We report on the cardiovascular effects observed in subjects exposed to hypoxia to illustrate the role of the sympathetic-adrenergic system in hypoxic syncope. This study describes unexpected episodes of (near) syncope during two crossover trials at simulated altitude in a low pressure chamber. METHODS: In study A, 30 healthy male volunteers underwent 4 exposures to short-term (20 min) acute severe hypoxia (20,000 ft or 6096 m) to assess psychological performance. In study B, five volunteers were studied during prolonged exposure (1 h) to moderate hypoxia (13,500 ft or 4115 m) with and without concomitant low dose infusion with atrial natriuretic peptide to investigate the effects on pulmonary gas exchange. RESULTS: In study A (acute severe hypoxia), 6 out of 120 exposures (5%), in 5 subjects, were accompanied by lightheadedness, pallor, sweating, and bradycardia. Two subjects (2%) had syncope with cardiac asystole. In study B during moderate hypoxia without atrial natriuretic peptide, adverse reactions were absent and the (nor)epinephrine levels remained unchanged. Concomitant infusion with atrial natriuretic peptide resulted in near syncope (recumbent in 3, standing in 2) at an oxygen saturation of 82%. While the epinephrine level had eightfold increased, mean arterial pressure fell from 94 to 40 mm Hg and heart rate from 79 to 44 bpm. The norepinephrine level remained unchanged illustrating a dissociated sympathetic-adrenergic response. All subjects with syncope recovered spontaneously within few minutes in Trendelenburg's position with oxygen supplied. None suffered from prolonged side effects. CONCLUSION: It is concluded that exposure to acute severe hypoxia is a sufficient cause for syncope in healthy individuals. Enhanced vasodilatation to epinephrine may contribute to the withdrawal of sympathetic and enhancement of parasympatic activity, leading to vascular collapse, bradycardia or asystole (Bezold-Jarisch reflex). Patients fully recover in Trendelenburg's position with supplemental oxygen and further clinical examinations are not necessary.     

Characterization of avian Chlamydia psittaci strains using omp1 restriction mapping and serovar-specific monoclonal antibodies

This study was carried out to evaluate the effect of continuous exposure to hypobaric hypoxia on the feeding behavior and taste responses of rats, under simulated conditions of a high altitude (HA) of 7,620 m for 21 h a day and consecutively for 18 d, which more closely resembles actual field conditions. Their food, water intake and body weight were recorded daily, and blood sugar was estimated once a week. All the parameters were recorded for a period of 18 d each, before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intake and body weight, and mild hypoglycemia during hypoxic exposure. Single-bottle and two-bottle tests showed a preference for sweet solutions over water, citric acid, sodium chloride, and quinine sulfate during exposure. The two-bottle test showed a preference for glucose over calorically-inert saccharine. The continuous exposure in this study produced qualitatively similar but quantitatively accentuated results as compared to intermittent 6 h exposure contiguously for 21 d. High-altitude stress appears to influence food intake such that sensory cues assume greater significance during feeding behavior.     

Long-lasting effect of prolonged hypoxemia after birth on the immediate ventilatory response to changes in arterial partial pressure of oxygen in young lambs

The effect of prolonged hypoxemia (H) after birth on the evolution of the ventilatory response to changes in arterial partial pressure of O2 was determined in unanesthetized, awake lambs. H was induced for 12 d after birth in seven lambs through exposure to 0.10 fraction of inspired O2 (FiO2). Five control (C) lambs were kept in 0.21 FiO2. The ventilatory response (percent increase from baseline) to acute hypoxia was tested with 0.14 FiO2 and 0.10 FiO2. The tonic activity of the peripheral chemoreceptors was assessed by the transient pure oxygen inhalation test (Dejours' test). The occlusion technique was used to measure the baseline neuromuscular drive of breathing. A markedly decreased early ventilatory response to acute hypoxia persisted in the H lambs for at least 5 wk after termination of H compared with the C group. The second phase of the response was significantly lower only at 12 d (the end of H) and was thereafter comparable to that in the C lambs. The ventilatory response to hyperoxia was significantly lower in the H lambs only at the end of hypoxemia at 12 d and rapidly normalized after return to normoxia. H did not significantly affect resting neuromuscular drive. These results show that postnatal maturation of the ventilatory response to changes in arterial partial pressure of O2 can be delayed by prolonged postnatal hypoxemia. The effect on the response to hyperoxia is transient, whereas the response to acute hypoxia is affected for an extended time. This study illustrates the importance of an adequate postnatal arterial partial pressure of O2 for the development of the ventilatory response to acute hypoxia.     

Effect of hemorrhagic hypotension on cortical oxygen pressure and striatal extracellular dopamine in cat brain

This study investigated the relationships between blood pressure, cortical oxygen pressure, and extracellular striatal dopamine in the brain of adult cats during hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the cortex was measured by the oxygen dependent quenching of phosphorescence and extracellular dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control) to 90 Torr, 70 Torr and 50 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. As the MAP was lowered there was a decrease in arterial pH, from a control value of 7.37 +/- 0.05 to 7.26 +/- 0.06. The PaCO2 decreased during bleeding from 32.3 +/- 4.8 Torr to 19.6 +/- 3.6 Torr and returned to 30.9 +/- 3.9 Torr after retransfusion. The PaO2 was 125.9 +/- 15 Torr during control conditions and did not significantly change during bleeding. Cortical oxygen pressure decreased with decrease in MAP, from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and 22 +/- 2 Torr, respectively. A statistically significant increase in striatal extracellular dopamine, to 2,580 +/- 714% of control was observed when MAP decreased to below 70 Torr and cortical oxygen pressure decreased to below 31 Torr. When the MAP reached 50 Torr, the concentration of extracellular dopamine increased to 18,359 +/- 2,764% of the control value. A statistically significant decrease in DOPAC and HVA were observed during the last step of bleeding. The data show that decreases in systemic blood pressure result in decrease in oxygen pressure in the microvasculature of the cortex, suggesting vascular dilation is not sufficient to result in a full compensation for the decreased MAP. The decrease in cortical oxygen pressure to below 32 Torr is accompanied by a marked increase in extracellular dopamine in the striatum, indicating that even such mild hypoxia can induce significant disturbance in brain metabolism.     

The effect of hypoxia on the regional distribution of cardiac output in the dog

Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.     

Study of platelet-activating factor acetylhydrolase in the perioperative period of patients undergoing cardiac surgery

This study was conducted to determine whether brief, intermittent exposure to hypoxia with little change in nutrient intake would affect fetal growth. Pregnant rats were exposed to 1 or 2 h of hypoxia (FiO2 = 0.09-0.095) from days 15 to 19 of gestation. Exposure to 1 h of hypoxia decreased fetal body weight and length, liver weight and increased the brain/liver weight ratio (p < 0.05) as compared to controls. Two hours of hypoxia decreased fetal body weight and length, and heart, lung, kidney, gut, brain and liver weights (p < 0.01), but did not affect the brain/liver weight ratio. Two hours of hypoxia decreased maternal food intake and weight gain (p < 0.05), but fetal growth was not significantly altered in pair-fed controls. These data demonstrate that brief, intermittent periods of intrauterine hypoxia have significant effects on fetal growth.     

Effects of physical training in a hypobaric chamber on the physical performance of competitive triathletes

The effects of training in a hypobaric chamber on aerobic metabolism were studied in five high performance triathletes. During 3 weeks, the subjects modified their usual training schedule (approximately 30 h a week), replacing three sessions of bicycling exercise by three sessions on a cycle ergometer in a hypobaric chamber simulating an altitude of 4,000 m (462 mm Hg). Prior to and after training in the hypobaric chamber the triathletes performed maximal and submaximal exercise in normoxia and hypoxia (462 mm g). Respiratory and cardiac parameters were recorded during exercise. Lactacidaemia was measured during maximal exercise. Blood samples were drawn once a week to monitor blood cell parameters and erythropoetin concentrations. Training in the hypobaric chamber had no effect on erythropoiesis, the concentrations of erythropoetin always remaining unchanged, and no effect on the maximal oxygen uptake (VO2max) and maximal aerobic capacity measured in normoxia or hypoxia. Submaximal performance increased by 34% during a submaximal exhausting exercise performed at a simulated altitude of 2,000 m. During a submaximal nonexhausting test, ventilation values tended to decrease for similar exercise intensities after training in hypoxia. The changes in these parameters and the improved performance found for submaximal exercise may have been the result of changes taking place in muscle tissue or the result of training the respiratory muscles.     

Effects of phenobarbital on cerebral blood flow during hypoxia

Phenobarbital (PB), at anticonvulsant dosages, has been used in an attempt to reduce hypoxic brain injury in asphyxiated newborn infants. The effects of PB pretreatment on the cerebral blood flow (CBF) response in hypoxia were studied in 15 curarized and mechanically ventilated piglets: 7 animals were pretreated with 20 mg/kg of PB (group 1) and 8 served as untreated controls (group 2). Successive aliquots (25 ml) of carbon monoxide were introduced into a closed ventilator circuit and CBF (measured with radiolabelled microspheres), arterial blood pressure, blood gases, arterial pH and PaO2 were subsequently determined at different levels of hypoxia. The amount of hemoglobin available for oxygen transport (i.e. total Hb-HbCO) was used to express hypoxic aggression and decreased from grade I (> 2 mmol/l) to grade II (1-2 mmol/l) to grade III (< 1 mmol/l). In the control group, CBF increased during grade-I hypoxia and continuously remained above baseline values during grade-II and grade-III hypoxia. In pretreated animals, however, only grade-II hypoxia was associated with a significant increase in CBF above baseline. In addition during grade-III hypoxia, CBF decreased to the prehypoxic values despite a fall in cerebral oxygen delivery and cardiac index. These data suggest that PB should be used with caution to prevent brain damage in the asphyxiated newborn infants.     

Lung hyaluronan and water content in preterm and term rabbit pups exposed to oxygen or air

Rabbit pups were delivered by cesarean section 1 or 2 d before term, or vaginally around term, and then reared in room air or exposed to intermittent or continuous hyperoxia (> 85%) for up to 9 d. Pups were killed at different ages, and lung hyaluronan (HA; microgram/g of dry lung weight) and lung water content, measured as wet/dry lung weight, were determined. Compared with the day of birth, the lung HA concentration did not change significantly on succeeding days in pups kept in air delivered 2 d (-2 d) or 1 d (-1 d) before term, whereas the water content decreased significantly. Continuous exposure to hyperoxia resulted in a significantly raised lung HA concentration 6 d postterm in both -2 d and -1 d pups, and intermittent exposure to hyperoxia resulted in a significantly raised HA concentration 6 d postterm in -1 d pups, compared with the groups exposed to room air. These increases were accompanied by significantly elevated wet/dry lung weight ratios. Microscopic examination revealed significantly increased HA staining scores in alveoli, arterioles, and bronchioli in both hyperoxia-exposed groups of -2 d pups 6 d postterm, and nonsignificantly higher scores in -1 d and vaginally delivered pups of comparable age, compared with the scores at birth. The results indicate that oxygen exposure neonatally may result in an increase in lung HA accompanied by an increase in lung water content. The increase in lung HA concentration in our study may be an effect of oxygen free radicals or of oxygen-induced stimulation of inflammatory mediators.     

Quantitative EEG in acute mountain sickness

OBJECTIVES: To investigate if the EEG response at moderate altitude may predict a person's tolerance to acute mountain sickness (AMS). MATERIALS AND METHODS: Frequency analysis (QEEG) of tape-recorded ambulatory EEG was performed in 6 climbers during a mountaineering expedition to 7546 m above sea level. The QEEG response in climbers, measured at sea level, at 4500 m, and at 1800 m 1-4 days after maximal altitude exposure, was compared to the change observed during consecutive sea level recordings in 10 control subjects. RESULTS: Three climbers experienced slight (grade 1) AMS symptoms both at 4500 m and at maximal altitude exposure (Group 1). Three other climbers (Group 2) had no symptoms at 4500 m, but they developed AMS (grades 1, 2, or 3) at maximal altitude. Alpha amplitudes were higher at 4500 m in group 1 climbers, while it was lower in group 2 climbers compared to the sea level recording. Significant time x group interactions in ANOVA were found for delta (P = 0.005), theta (P = 0.001) and alpha (P = 0.001) amplitude, indicating that QEEG amplitudes decreased significantly at high altitude in group 2 climbers. CONCLUSION: The QEEG response to moderate hypobaric hypoxia is not uniform, but the direction of QEEG amplitude change, particularly in the alpha band, may possibly predict the risk of developing AMS.     

Glutathione, a biochemical indicator for different types of cellular stress. The change in the GSH level in the brain of rats with hypoxia]

By the ligation of left vertebral artery in some white, adult WISTAR rats, of 150-200 g, anaesthetized with ether, a cerebral hypoxia of 10 minutes was induced. After beheading, there was determined the level of SH-neproteic groups and glutathione (GSH) in the whole heparinized blood and there was observed an important decrease with -15.88% and -16.80% respectively, in comparison with the normal lot (100%), kept under the some laboratory conditions. The GSH level in the neural cytosol is also significantly decreased with -8.66% in rats with hypoxia. The GSH depletion in the induced hypoxia, by our experiment, might be due to the reaction between nitric oxide (NO.) radical and intracellular GSH (blood and neuronal cytosol), considering the literature in this field, and S-nitrosoglutathion (S-NO-GSH) bioactive intermediary is formed and it protects the hypoxied brain against the NO.-dependent cytotoxicity, in the initial phase of hypoxia. The decrease of GSH and SH-neproteic groups level is considered a biochemical marker of the growth of the free radicals level to O2 (NO., O2., OH., H2O2, 1O2), that appear in the hypoxic and/or ischemic stress, but also a major sign in the rol of "scavenger" and antioxidant of the radicals at the cerebral and sanguine level, in the above mentioned conditions.     

Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat

Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular matrix protein synthesis in response to hemodynamic stress, regresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and elastase in pulmonary arteries of rats exposed to hypoxia (10% O2 for 10 d) followed by normoxia. During hypoxia, contents of collagen and elastin increased in pulmonary arteries and latent rat interstitial collagenase was expressed without increased collagenolytic activity or mRNA levels. At 3 days after normoxia, collagen and elastin contents decreased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in connective tissue-type mast cells, was increased in the adventitia and media of hypertensive vessels. We conclude that mast cells containing latent collagenase are recruited into the outer walls of pulmonary arteries during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular architecture.     

The effect of the combined treatment of patients with postradiation encephalopathy on lipid peroxidation activity

Conventionally healthy persons-donors and diseased subjects who had taken part in the elimination of the Chernobyl accident effects were evaluated for the activity of the process of free radical lipid peroxidation (LPO). The patient population demonstrated a significant elevation of blood levels of malonic dialdehyde, enhancement of intensity of spontaneous chemoluminescence together with a decrease in resistance of red cells to oxide. After the general course of therapy involving use of enterosorbents, antioxidants, and normobaric intermittent hypoxia, there was an appreciable decrease in the blood plasma LPO intensity, which observation was accompanied with improvement in general health of the patients.